The nephrotoxicity of aminoglycoside such as gentamicin which is generally used in severe infections including gram-negative bacterial infection, has been a problem in clinical stting. To treat the infected patients with these agents
aggressively,
we
need a method to prevent those nephrotoxicity. The study of continuous urinary alkalinization during the gentamicin therapy in Fischer 344 rate with regular renal function measurements suggested that it could reduce the nephrotoxicity of
gentamicin. To
evaluate the preventive effects in human, we studied the effect of continuous urinary alkalinization on gentaiin nephrotoxicity in patients who had normal renal function and in whom gentamicin was indicated for their infections. We divided the
patients
into three groups randomly. The first group was given gentamicin(3mg/kg/day) only (control group), the second group given gentamicin (3mg/kg/day) and sodium bicarbonate (6g/day), and the third group given gentamicin(3mg/kg/day), sodium
bicarbonate
(6g/day) and acetazolamide (1 g/day). Bun, serum creatinine ratio were measured before, during and after therapy.
1) Total 76 patients (14 males and 62 females) were studied. The mean age was 39.5±16.0 years in group 1, 35.7±14.4 in group 2, and 38.1±13.8 in group 3, which were not significantly different. The infections of those 76 patients were acute
pyelonephritis in 50 cases, acute cystitis in 9 cases, pneumonia in 6 cases, gastroenteritis in 3 cases, salmonellosis in 2 cases, and others in 8 cases.
2) Urine pH in each group before therapy were 6.19±1.03 in group 1, 5.57±0.83 in group 2, 5.98±0.98 in group 3. Significant urinary alkalinizations were noted in group 2 and 3 in which the urinary pH on the 7th ad 14th day after gentamicin
therapy
were 6.74±1.29 and 7.04±1.33 in group 2, and 6.88±1.33 and 6.93±1.27 in group 3, compared with 6.04±0.89 and 5.56±0.91 in group 1(p<0.05).
3) The increase in serum creatinine greater than 20% of baselinevalue was noted in 10.7%(3/28 patients) of group 1, 4.5%(1/22 patients) of group 2, and 19.0%(4/21 patients) of group 3 on the 7th day of therapy, and 20.0%(2/10 patients),
20.0%(3/15
patients) and 13.3%(2/15 patients) in each group on the 14th day.
4) The creatinine clearance (ml/min/1.73m2) before, on the 7th and 14th day after therapy were 92.33±39.71, 98.79±33.54 and 102.49±24.11 in group 1, 99.05±37.07, 93.84±27.37 and 94.13±30.78 in group 2, and 87.62±34.82, 87.54±32.71 and
88.58±29.74 in group 3. And there was no significant difference.
5) The baseline ratio of β2-MG/creatinine in urine on the 3rd, 7th and 14th day after terapy were 1.61±2.62, 19.09±52.34 and 79.25±242.48 in group 1, 1.44±2.24, 11.86±30.98 and 39.78±137.7 in group 2, and 1.44±1.23, 4.62±10.39 and
5.63±11.57
in group 3. The baseline ratio of β2 -MG/creatinine was decreased to 15.97±43.10, 4.58±7.89 and 1.93±3.56 in each group on 3days after the end of the therapy.
In conclusion, urinary alkalinization showed the tendency of preventive effects on gentamicin nephrotoxicity in human, but follow up studies on the patients with high risks for the amonglycoside nephrotoxicity would be needed to define more
definite
preventive effects of urinary alkalinization of these patients.
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